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Related Concept Videos

Tumor Progression02:07

Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Mutations01:35

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Gain and phase shift are properties of linear circuits that describe the effect a circuit has on a sinusoidal input voltage or current. The circuit's behavior that contains reactive elements will depend on the frequency of the input sinusoid. As a result, it is observed that the gain and phase shift will all be frequency functions.
Gain:
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Metallic solids such as crystals of copper, aluminum, and iron are formed by metal atoms. The structure of metallic crystals is often described as a uniform distribution of atomic nuclei within a “sea” of delocalized electrons. The atoms within such a metallic solid are held together by a unique force known as metallic bonding that gives rise to many useful and varied bulk properties.
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Biallelic TP53 gain of function mutations in rapidly progressing solid tumors.

Christopher M Sande1, Brian Chang1, Varun Monga2

  • 1Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USA.

Cancer Genetics
|April 19, 2018
PubMed
Summary
This summary is machine-generated.

This study identified rare biallelic TP53 mutations with gain of function (GOF) properties in tumors, impacting patient outcomes. Targeting GOF p53 may offer new therapeutic strategies for cancer.

Keywords:
Gain of function mutationNext generation sequencingTP53

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • TP53 mutations with gain of function (GOF) properties are increasingly recognized for their role in promoting tumorigenesis.
  • Previous reports of compound TP53 mutations have been exclusively allelic.

Observation:

  • This study identified two patients with biallelic GOF TP53 mutations and one with compound allelic variants in their tumors.
  • Biallelic GOF mutations (p.R273H and p.R273C) were found in glioblastoma and penile squamous cell carcinoma.
  • A third patient presented with allelic GOF (p.P278S) and non-GOF (p.R283L) variants in metastatic lung adenocarcinoma.

Findings:

  • Immunohistochemistry revealed nuclear p53 accumulation in patients with biallelic GOF mutations.
  • The patient with allelic GOF and non-GOF variants showed null p53 staining.
  • All identified patients succumbed to their disease within two years, irrespective of treatment.

Implications:

  • TP53 mutation analysis in clinical settings may serve as a prognostic indicator for patient outcomes.
  • Inhibiting GOF p53 presents a promising therapeutic target for various cancers.
  • The identification of biallelic GOF TP53 mutations broadens our understanding of tumor suppressor gene behavior.